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Mycobacterial Small Heat Shock Proteins: Dissecting Their Roles in Pathogenesis and Development of Therapeutics
Subhashree Barik1, Pulak Pritam2, Ayon Chakraborty3
1School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar 752050, India.
Abstract:
Small heat shock proteins are a ubiquitous family of molecular chaperones. This class of proteins has a conserved α-crystallin domain. Mycobacterium tuberculosis, the etiological agent that causes tuberculosis (TB), harbors two α-crystallin-related (Acr) small heat shock proteins, Acr1 (Hsp16.3) and Acr2 (HrpA). Both of these proteins have been reported as crucial for the survival and pathogenesis of M. tuberculosis inside the host. Acr1 often plays a critical role in the pathogen's survival in the latent stage, while Acr2 overexpresses following phagocytosis during the active infection and is also required for pathogenesis. The strong immunogenicity of Acr1 and Acr2 has been utilized for developing and boosting vaccines and as a diagnostic marker for active and latent TB. Some recent studies have also implicated the development of drugs against these small heat shock proteins. In addition, several structure-function studies established the role of different stresses on the structure and function of these proteins. However, such studies on Acr2 are few in the literature. In this review, the various biophysical and early diagnostic studies of Acr1 and Acr2 are presented systematically. Subsequently, the role of these Acrs in pathogenesis and toward the development of vaccines against TB is discussed.
Insights
Tuberculosis (TB) involves two small heat shock proteins, Acr1 and Acr2, crucial for pathogen survival and disease. Research reviews their roles in TB pathogenesis and potential as vaccine targets.
Area of Science:
- Microbiology
- Immunology
- Biochemistry
Background:
- Small heat shock proteins (sHSPs) are molecular chaperones with a conserved α-crystallin domain.
- Mycobacterium tuberculosis (TB) possesses two α-crystallin-related (Acr) sHSPs: Acr1 (Hsp16.3) and Acr2 (HrpA).
- Both Acr1 and Acr2 are vital for M. tuberculosis survival and pathogenesis within the host.
Purpose of the Study:
- To systematically review biophysical and early diagnostic studies of Acr1 and Acr2.
- To discuss the roles of Acr1 and Acr2 in TB pathogenesis.
- To explore the potential of Acr1 and Acr2 in the development of TB vaccines.
Main Methods:
- Literature review of biophysical studies.
- Analysis of diagnostic studies.
- Review of research on Acr1 and Acr2 in pathogenesis and vaccine development.
Main Results:
- Acr1 is critical for latent TB survival; Acr2 is upregulated during active infection and essential for pathogenesis.
- Acr1 and Acr2 are immunogenic, making them potential vaccine candidates and diagnostic markers.
- Structure-function studies highlight the impact of stress on Acr1 and Acr2, though Acr2 has fewer related studies.
Conclusions:
- Acr1 and Acr2 are key virulence factors in M. tuberculosis.
- These proteins hold significant promise for novel TB vaccine development and diagnostics.
- Further research into Acr2's structure-function relationship is warranted.
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